A new class of inhibitors of 2-arachidonoylglycerol hydrolysis and invasion of prostate cancer cells. Biochem Biophys Res Commun 2005 Jul 15;332(4):1028-33
Date
05/28/2005Pubmed ID
15919052Pubmed Central ID
PMC1450257DOI
10.1016/j.bbrc.2005.05.049Scopus ID
2-s2.0-20444399512 (requires institutional sign-in at Scopus site) 49 CitationsAbstract
Endogenous 2-arachidonoylglycerol (2-AG) inhibits invasion of androgen-independent prostate cancer cells. Blocking cellular hydrolysis of 2-AG to increase its endogenous concentration results in a decrease in cell invasion. A series of compounds containing a trifluoromethyl ketone (TFK) moiety or the methyl analog (known to inhibit carboxylesterases) were investigated for their ability to inhibit 2-AG hydrolysis and prostate cancer cell invasion. Compounds containing a thioether beta to a TFK moiety inhibited 2-AG hydrolysis as well as cell invasion in a concentration-dependent manner. Inhibition of 2-AG hydrolysis increased concomitantly with inhibitor alkyl chain length from 4- to 12-carbons while inhibition of cell invasion exhibited a maximum at 8- to 10-carbons of the compounds. These results demonstrate a new series of 2-AG hydrolysis inhibitors as a potential therapeutic approach for prostate cancer.
Author List
Nithipatikom K, Endsley MP, Isbell MA, Wheelock CE, Hammock BD, Campbell WBAuthor
William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Antineoplastic AgentsArachidonic Acids
Cannabinoid Receptor Modulators
Cell Line, Tumor
Chromatography, Liquid
Collagen
Dose-Response Relationship, Drug
Drug Combinations
Endocannabinoids
Enzyme Inhibitors
Glycerides
Humans
Hydrolysis
Ketones
Laminin
Male
Models, Chemical
Neoplasm Invasiveness
Prostatic Neoplasms
Proteoglycans
Spectrometry, Mass, Electrospray Ionization
Sulfides
